New drug combo causes cancer cells to 'eat themselves'

PTI | Nov 6, 2013, 03.59 PM IST

WASHINGTON: A new drug combination therapy could effectively kill colon, liver, lung, kidney, breast and brain cancer cells without affecting the healthy cells, scientists say.

The results from a recent preclinical study at Virginia Commonwealth University Massey Cancer Center lays the foundation to plan a future phase 1 clinical trial to test the safety of the therapy in a small group of patients.

"It is still too premature to estimate when a clinical trial will open to further test this drug combination therapy, but we are now in the planning phase and encouraged by the results of these laboratory experiments," said Andrew Poklepovic, assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine.

The study led by Paul Dent demonstrated that the drugs sorafenib and regorafenib synergise with a class of drugs known as PI3K/AKT inhibitors to kill a variety of cancers.

Sorafenib and regorafenib work by blocking the production of enzymes called kinases, which are vital to the growth and survival of cancer cells.

Sorafenib is currently approved by the FDA to treat kidney and liver cancers, and regorafenib is currently approved for the treatment of colorectal cancer.

However, sorafenib and regorafenib do not directly affect PI3K and AKT kinases, which are also very active in promoting cancer cell survival.

The addition of a PI3K/AKT inhibitor to the combination of sorafenib and regorafenib dramatically increased cell death and was even effective against cells with certain mutations that make one or the other drug less effective.

"We know that there are certain cellular processes that are frequently dysregulated in cancers and important to cell proliferation and survival, but if you shut down one, then cells can often compensate by relying on another," said Dent.

"We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive," Dent said.

Results showed that the combination therapy killed the cells by physically interacting with molecules to block the survival pathways and induce a toxic effect known as autophagy.

Autophagy is a protective process where cells metabolise themselves when starved of the resources needed to survive.

The study was published in the journal Molecular Pharmacology.

sight is really as much a function of our brains as our eyes,RELATED People born blind can see during a near-death experience

Brain can 'see' in the dark: Study

PTI | Nov 3, 2013, 06.06 AM IST

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At least 50 per cent of people can see the movement of their own hand even when it is pitch dark, a new study said.

People born blind can see during a near-death experience

www.near-death.com/experiences/evidence03.html‎

Yet, she appears to have been able to see during her NDE. ... roof of the building itself, during which time she had a brief panoramic view of her surroundings.

WASHINGTON: At least 50 per cent of people can see the movement of their own hand even when it is pitch dark, a new study, that used computerised eye-trackers, has found.

Even in the absence of all light, the brain keeps track of the body, researchers said.

Neuroscientists and psychologists discovered that the mind continues to perceive motion in complete darkness. Their findings suggest that 50 per cent of the population sees in the dark without realising it.

"Seeing in total darkness? According to the current understanding of natural vision, that just doesn't happen," says Duje Tadin, a professor of brain and cognitive sciences at the University of Rochester who led the investigation.

"But this research shows that our own movements transmit sensory signals that also can create real visual perceptions in the brain, even in the complete absence of optical input," said Tadin.

Through five separate experiments involving 129 individuals, the authors found that this eerie ability to see our hand in the dark suggests that our brain combines information from different senses to create our perceptions.

The ability also "underscores that what we normally perceive of as sight is really as much a function of our brains as our eyes," said first author Kevin Dieter, a post-doctoral fellow in psychology at Vanderbilt University.

For most people, this ability to see self-motion in darkness probably is learned, the authors conclude.

"We get such reliable exposure to the sight of our own hand moving that our brains learn to predict the expected moving image even without actual visual input," said Dieter.

The study was published in journal Psychological Science.

Left or right wagging tail means different things among dogs

Subodh Varma, TNN | Nov 1, 2013, 04.01 PM IST

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There is more to the dog wagging its tail than meets the eye, scientists have found. The rightward wag and the leftward wag mean different things to dogs. This happens because dogs, like humans, have asymmetrically organized brains, with the left and right sides playing different roles, thescientific study published in the journal Current Biology on Thursday, suggests.

The Italian research team led by Giorgio Vallortigara of the Center for Mind/Brain Sciences of the University of Trento had earlier found that dogs wag to the right when they feel positive emotions (upon seeing their owners, for instance) and to the left when they feel negative emotions (upon seeing an unfriendly dog, for example). That biased tail-wagging behavior reflects what is happening in the dogs' brains. Left-brain activation produces a wag to the right, and right-brain activation produces a wag to the left.

But does that tail-wagging difference mean something to other dogs? Yes it does, the new study shows.

While monitoring their reactions, the researchers showed dogs videos of other dogs with either left- or right-asymmetric tail wagging. When dogs saw another dog wagging to the left, their heart rates picked up and they began to look anxious. When dogs saw another dog wagging to the right, they stayed perfectly relaxed.

"The direction of tail wagging does in fact matter, and it matters in a way that matches hemispheric activation," says Vallortigara.

A right wag means the left hemisphere of the brain is activated in the dog. That means it is experiencing some positive response. So, another dog observing it would feel a relaxed response. In contrast, a dog showing a left wag activated by the right hemisphere is feeling a negative or withdrawal response. To the observing dog, this would induce an anxious and targeting response as well as increased cardiac frequency.

Vallortigara doesn't think that the dogs are necessarily intending to communicate those emotions to other dogs. Rather, he says, the bias in tail wagging is likely the automatic byproduct of differential activation of the left versus the right side of the brain. But that's not to say that the bias in wagging and its response might not find practical uses; veterinarians and dog owners might do well to take note.